MRI assessment of pituitary iron accumulation by using pituitary-R2 in β-thalassemia patients

Abstract

Background

Patients with thalassemia major (TM) require repeated blood transfusions, which leads to accumulation of iron in a wide variety of tissues. Accumulation of iron in the pituitary gland can lead to irreversible hypogonadotropic hypogonadism (HH) in this group of patients.

Purpose

To investigate the reliability of pituitary-R2 as a marker to estimate the extent of pituitary iron load by comparing the pituitary magnetic resonance imaging (MRI) findings with hepatic iron load and serum ferritin levels.

Material and Methods

A total of 38 β-TM patients were classified into HH (group A, n = 18) and non-HH (group B, n = 17) groups. A third group, group C, consisted of 17 healthy participants. Each participant underwent 1.5-T MRI examinations. Pituitary gland heights (PGH), pituitary-R2 values, and liver-R2 values were measured by using multi-echo spin-echo sequences.

Results

Pituitary-R2 values were significantly higher in group A compared with group B (P < 0.05). A positive correlation was detected between the pituitary-R2 values and serum ferritin levels in TM patients (P < 0.01). A threshold value of 14.1 Hz for pituitary-R2 was found to give a high specificity and sensitivity in distinguishing the TM patients with HH from those with normal pituitary functions. PGH measurements were significantly lower in group A compared with group B (P < 0.05).

Conclusion

MRI-assessed pituitary-R2 seems to be a reliable marker for differentiating the TM patients with normal pituitary function from those with secondary hypogonadism due to iron toxicity.

Keywords

β-thalassemia hypogonadotropic hypogonadism iron load magnetic resonance imaging (MRI)pituitary gland

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References

Rund

Rachmilewitz

. Beta-thalassemia. N Engl J Med 2005; 353: 1135–1146.

Canatan

Kose

Ustundag

et al.

Hemoglobinopathy control program in Turkey. Community Genet 2006; 9: 124–126.

St Pierre

Clark

Chua-anusorn

et al.

Non invasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 2005; 105: 855–861.

Anderson

Holden

Davis

et al.

Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J 2001; 22: 2171–2179.

Wood

Noetzl

Hyderi

et al.

Predicting pituitary iron and endocrine dysfunction. Ann N Y Acad Sci 2010; 1202: 123–128.

Tsunoda

Okudo

Sato

. MR height of the pituitary gland as a function of age and sex: especially physiological hypertrophy in adolescene and in climacterium. Am J Neuroradiol 1997; 18: 551–554.

Alexopoulou

Stripeli

Baras

et al.

R2 relxometry with MRI for the quantification of tissue iron overload in beta-thalassemic patients. J Magn Reson Imaging 2006; 23: 163–170.

Noetzli

Panigrahy

Mittelman

et al.

Pituitary iron and volume predict hypogonadism in transfusional iron overload. Am J Hematol 2012; 87: 167–171.

Borgna-Pignatti

Rugolotto

De Stefano

et al.

Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 2004; 89: 1187–1193.

10.

Chavgan

Babyn

Thomas

et al.

Principles, techniques, and applications of T2*-based MR imaging and its special applications. Radiographics 2009; 29: 1433–1449.

11.

Wood

Ghurge

. MRI assessment of excess iron in thalassemia, sickle cell disease and other iron overload diseases. Hemoglobin 2008; 32: 85–96.

12.

Argyropoulou

Metafratzi

Kiortsis

et al.

T2 relaxation rate as an index of pituitary iron overload in patients with beta-thalassemia major. Am J Roentgenol 2000; 175: 1567–1569.

13.

Hekmatnia

Radmard

Rahmani

et al.

Magnetic resonance imaging signal reduction may precede volume loss in the pituitary gland of transfusion-dependent beta-thalassemic patients. Acta Radiol 2010; 51: 71–77.

14.

Noetzli

Panigrahy

Hyderi

et al.

Pituitary iron and volume imaging in healthy controls. Am J Neuroradiol 2012; 33: 259–265.

15.

Argyropoulou

Kiortsis

Efremidis

. MRI of the liver and the pituitary gland in patients with beta-thalassemia major: does hepatic siderosis predict pituitary iron deposition? Eur Radiol 2003; 13: 12–16.

16.

Atkin

Burnett

Green

et al.

Expression of the transferrin receptor in human anterior pituitary adenomas is confined to gonadotrophinomas. Clin Endocrinol (Oxf) 1996; 44: 467–471.

17.

Thorstensen

Trinder

Zak

et al.

Uptake of iron from N-terminal half-transferrin by isolated rat hepatocytes. Evidence of transferrin-receptor-independent iron uptake. Eur J Biochem 1995; 232: 129–133.

18.

Argyropoulou

Kiortsis

Metafratzi

et al.

Pituitary gland height evaluated by MR in patients with beta-thalassemia major: A marker of pituitary gland function. Neuroradiology 2001; 43: 1056–1058.

19.

Argyropoulou

Kiortsis

Astrakas

et al.

Liver, bone marrow, pancreas and pituitary gland iron overload in young and adult thalassemic patients: a T2 relaxometry study. Eur J Radiol 2007; 17: 3025–3030.

20.

Srisukh

Boonsong

Pongamorn

. Hypogonadism in thalassemia major patients. J Clin Transl Endocrinol 2016; 5: 42–45.

21.

Christoforidis

Haritandi

Perifanis

et al.

MRI for the determination of pituitary iron overload in children and young adults with beta-thalassaemia major. Eur J Radiol 2007; 62: 138–142.

22.

Gamberini

De Sanctis

Gilli

. Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre. Pediatr Endocrinol Rev 2008; 6 Suppl: 158–159.

23.

Hoffbrand

Taher

Cappellini

. How I treat transfusional iron overload. Blood 2012; 120: 3657–3669.